Molecular Mechanism and Energy Basis of Conformational Diversity of Antibody SPE7 Revealed by Molecular Dynamics Simulation and Principal Component Analysis

Abstract

More and more researchers are interested in and focused on how a limited repertoire of antibodies can bind and correspondingly protect against an almost limitless diversity of invading antigens. In this work, a series of 200-ns molecular dynamics (MD) simulations followed by principal component (PC) analysis and free energy calculations were performed to probe potential mechanism of conformational diversity of antibody SPE7. The results show that the motion direction of loops H3 and L3 is different relative to each other, implying that a big structural difference exists between these two loops. The calculated energy landscapes suggest that the changes in the backbone angles ψ and φ of H-Y101 and H-Y105 provide significant contributions to the conformational diversity of SPE7. The dihedral angle analyses based on MD trajectories show that the side-chain conformational changes of several key residues H-W33, H-Y105, L-Y34 and L-W93 around binding site of SPE7 play a key role in the conformational diversity of SPE7, which gives a reasonable explanation for potential mechanism of cross-reactivity of single antibody toward multiple antigens.

In silico assessment of the inhibitory effect of four flavonoids (Chrysin, Naringin, Quercetin, Kaempferol) on tyrosinase activity using the MD simulation approach

“…The Rg time graph showed that residual backbone and the folding of the receptor protein were steadily stable after the binding of inhibitors, which confirmed our results (Hassan et al, 2018). The RMSF value provides a better understanding of the protein flexibility and structural fluctuations (Chen et al, 2016;Mahapatra et al, 2018). To define the flexible regions of the enzyme in the enzyme-substrate/inhibitor complexes, the RMSF values of Cα atoms of the protein were evaluated.…”

“…Finally, the PMF pattern was provided by the Weighted Histogram Analysis (WHAM) method, which was carried out by GROMACS as "g_wham" command (Zeng et al, 2016). Moreover, for a better recognition of the MD process, the RMSF (root mean square fluctuation) (Chen et al, 2016;Mahapatra et al, 2018), RMSD (root mean square deviation) (Kaur et al, 2019;Shen et al, 2012), Rg (Radius of gyration) (Anantram et al, 2018;Farasat et al, 2017;Lobanov et al, 2008), the inhibitor and substrate distance from the amino acids of the enzyme active site (Corvo et al, 2013;Kato et al, 2017), and the van der Waals and the electrostatic energy of each system were analyzed using GROMACS tools in the period of simulation (Fried and Boxer, 2017;Schutt et al, 2015). Eventually, the final PDB file of MD simulation was plotted using Pymol software (Stourac et al, 2019).…”

Effects of unsaturated fatty acids (Arachidonic/Oleic Acids) on stability and structural properties of Calprotectin using molecular docking and molecular dynamics simulation approach

“…The results showed that RMSD value of the Calprotectin alone was greater than the Calprotectin-UFAs complexes which confirms the structural changes of the Calprotectin in presence of fatty acids. RMSF value provides a better understanding of the protein flexibility and structural fluctuations [37,38]. To study the Calprotectin flexibility in presence of AA and OA, the RMSF value was calculated for Calprotectin, Calprotectin-AA and Calprotectin-OA during the simulation.…”

Enfuvirtide, an HIV-1 fusion inhibitor peptide, can act as a potent SARS-CoV-2 fusion inhibitor: an in silico drug repurposing study

“…RMSF comprises a valuable parameter which allows for a more proper understanding of protein flexibility and structural fluctuations (Chen et al., 2016 ; Mahapatra et al., 2018 ). RMSF was calculated to evaluate the flexibility of the S2 protein in the presence or absence of the peptide (Enf).…”